The goal of this research is to provide a comprehensive analysis of the total electric field (E-field) induced in neural tissues by transcranial magnetic stimulation (TMS) and its efficacy in producing explicit neuronal activations. Currently, the mechanisms of action underlying TMS induced brain stimulations are not well understood, thus experimentation rather than a solid theoretical model determines many of the treatment parameters-such as stimulator intensity, rate and treatment duration. By modeling the total E-fields induced by TMS, we can shed light on the specific mechanisms involved in TMS induced brain stimulations. The objective of the experiments proposed here is to test (and possibly refine) mathematically formulated hypotheses governing the relationship between the E-fields induced by TMS and any local cortical responses resulting from exposure to these induced E-fields. Once this is done both the delivery and quantitative assessment of each TMS pulse can be improved-expanding TMS'use as a non-invasive biomedical device. In Specific Aim 1, the applicant will use magnetic resonance imaging techniques to obtain subject-specific head images-characterizing the geometric size, shape and electrical conductivity of each subject's head. In Specific Aim 2, the applicant will examine the effects of modulating TMS intensity, orientation and pulse waveform on measured electromyographic (i.e. EMG) responses. EMG response magnitude should vary as a function of the induced E-field vector relative to the direction of the cortical column (resulting in an effective E- field). Specific Aim 3 focuses on calculating accurate, four-dimensional (i.e. space and time) models of the total and effective E-fields induced by TMS in a realistic head model. The subject-specific head models created in Aim 1 will be used in numerical calculations--i.e. the finite element method--then compared to the EMG responses (Aim 2) to elaborate on the efficacy of each TMS treatment parameter. Accurate models of TMS induced neuronal activations will increase the effectiveness of any TMS experiment-ultimately leading to better clinical/research use. PUBLIC HEALTH RELEVANCE: Transcranial magnetic stimulation (TMS) is primarily used as a noninvasive therapeutic treatment of psychiatric disorders such as depression, schizophrenia, and anxiety;TMS is also effective in assessing drug- related effects on the central nervous system. TMS is also being used as a diagnostic tool, allowing quantitative assessments of the motor deficits involved in multiple sclerosis, Parkinson's disease, and the effects of stroke. By the modeling the electric fields produced by TMS we can better understand the mechanisms of neuronal activation, including how a particular disease/disorder may be affecting the nervous system.